FTY720P inhibits the Na+/K+ ATPase in Caco-2 cells via S1PR2: PGE2 and NO are along the signaling pathway

Rida, Reem; Kreydiyyeh, Sawsan Ibrahim

doi:10.1016/j.lfs.2018.11.026

Cited by 9 publications

(13 citation statements)

References 31 publications

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“…A similar inhibitory effect of PGE2 on the Na + /K + ATPase was observed in another work [11] in which PGE2 release was induced by FTY720P. The prostaglandin there reduced the activity of the ATPase by activating however EP3 and not EP1 receptors.…”

Section: Discussionsupporting

confidence: 81%

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The epinephrine-induced PGE2 reduces Na+/K+ ATPase activity in Caco-2 cells via PKC, NF-κB and NO

2019

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We showed previously an epinephrine-induced inhibition of the Na + /K + ATPase in Caco-2 cells mediated via PGE2. This work is an attempt to further elucidate mediators downstream of PGE2 and involved in the observed inhibitory effect. The activity of the Na + /K + ATPase was assayed by measuring the amount of inorganic phosphate liberated in presence and absence of ouabain, a specific inhibitor of the enzyme. Changes in the protein expression of the Na + /K + ATPase were investigated by western blot analysis which revealed a significant decrease in the abundance of the ATPase in plasma membranes. Treating the cells with epinephrine or PGE2 in presence of SC19220, a blocker of EP1 receptors abolished completely the effect of the hormone and the prostaglandin while the effect was maintained unaltered in presence of antagonists to all other receptors. Treatment with calphostin C, PTIO, ODQ or KT5823, respective inhibitors of PKC, NO, soluble guanylate cyclase and PKG, abrogated completely the effect of epinephrine and PGE2, suggesting an involvement of these mediators. A significant inhibition of the ATPase was observed when cells were treated with PMA, an activator of PKC or with 8-Br-cGMP, a cell permeable cGMP analogue. PMA did reduce the protein expression of IκB, as shown by western blot analysis, and its effect on the ATPase was not manifested in presence of an inhibitor of NF-κB while that of SNAP, a nitric oxide donor, was not affected. The results infer that NF-κB is downstream PKC and upstream NO. The data support a pathway in which epinephrine induces the production of PGE2 which binds to EP1 receptors and activates PKC and NF-κB leading to NO synthesis. The latter activates soluble guanylate cyclase resulting in cGMP production and activation of PKG which through direct or indirect phosphorylation inhibits the Na + /K + ATPase by inducing its internalization.

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Section: Discussionsupporting

confidence: 81%

“…In many previous works, we showed that PGE2 modulates the activity of the Na + /K + ATPase via nitric oxide (NO) [5,6]. In this work also, epinephrine and PGE2 did not exert their effect in presence of PTIO (Fig 4A and 4B), a scavenger of NO.…”

Section: Resultssupporting

confidence: 55%

The epinephrine-induced PGE2 reduces Na+/K+ ATPase activity in Caco-2 cells via PKC, NF-κB and NO

2019

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“…From the perspective of modern pharmacology, the baicalein in Scutellaria effectively regulates interleukin-1β and accelerates the production of PGE2. Research by Ji et al showed that Dahuang-Huanglian-Xiexin Decoction based on rhubarb and Scutellaria could increase the level of PGE2 in the gastric tissue of rats with gastric ulcers [28], enhance the gastric mucosal protective mechanism, reduce gastric acid secretion, and inhibit the release of cytotoxic substances and lysosomal enzymes, resulting in a better gastric mucosal repair [29,30]. Roasted Astragalus regulates the secretion of Th-type cytokines such as tumor necrosis factor and interleukin-1 and mitigates their damage to endothelial cells, facilitating the synthesis and release of NO from vascular endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

A Retrospective Trial Exploring Erzhu Yiren Decoction in Gastric Ulcer with Spleen Deficiency and Dampness-Heat

Zhang

Zhaowei

2022

BioMed Research International

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Objective. To assess the efficacy of Erzhu Yiren Decoction in treating gastric ulcer of spleen deficiency and dampness-heat and its effect on serum NO, EGF, and PGE2 levels. Methods. A retrospective study was conducted among 64 patients with gastric ulcers of spleen deficiency and dampness heat admitted to our hospital from September 2019 to May 2020, and they were divided at a ratio of 1 : 1 into an observation group (rabeprazole sodium enteric-coated capsules plus Erzhu Yiren Decoction) and a control group (rabeprazole sodium enteric-coated capsules) based on different treatment methods. The clinical symptom scores, the effective rate of ulcer healing under gastroscopy, the quality of ulcer healing (QOUH), serum nitric oxide (NO), endothelial growth factor (EGF), and prostaglandin E2 (PGE2) levels were compared between the two groups. Results. The clinical symptom scores of the observation group after treatment were significantly lower than those of the control group ( P < 0.001 ). The observation group obtained a remarkably higher efficacy of ulcer healing under gastroscopy than the control group ( P = 0.039 ). The observation group outperformed the control group in terms of the number of patients with excellent and good QOUH ( P = 0.003 , 0.014), but no statistical difference in the number of patients with poor QOUH between the two groups was found ( P > 0.05 ). Serum NO, EGF, and PGE2 levels of the observation group after treatment were significantly better than those of the control group ( P < 0.001 ). Conclusion. Erzhu Yiren Decoction can relieve the clinical symptoms of patients with gastric ulcers of spleen deficiency and dampness heat; improve the serum NO, EGF, and PGE2 levels; optimize the mucosal maturity; and enhance the overall efficacy, which merits clinical promotion.

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“…If FTY720P has a similar activity profile to that of S1P, then we would expect it to exert a dual and opposite time dependent effect on the ATPase leading to time dependent alterations in liver activities. We demonstrated previously in Caco-2 cells [11] and in HepG2 cells [12,13], a significant FTY720P-induced inhibition of the Na + /K + ATPase at 15min whether at two hours FTY720P exerts in HepG2 cells, like S1P, a stimulatory effect is a question that we aim to address in this work. This work is thus a follow up and a continuation of the previous one and is undertaken to complete the time course study.…”

Section: Introductionmentioning

confidence: 88%

“…Treatment of HepG2 cells with FTY720-P HepG2 cells were treated for 2 hours with 7.5 nM FTY720-P, a concentration that showed in a previous work [11] a significant inhibitory effect at 15 min. An equal volume of the vehicle (DMSO) was added to the control.…”

Section: Culture Of Hepg2 Cellsmentioning

confidence: 99%

FTY720P Upregulates the Na+/K+ ATPase in HepG2 Cells by Activating S1PR3 and Inducing PGE2 Release

Chakkour

Kreydiyyeh

2019

Cell Physiol Biochem

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FTY720P inhibits the Na+/K+ ATPase in Caco-2 cells via S1PR2: PGE2 and NO are along the signaling pathway

Cited by 9 publications

References 31 publications

The epinephrine-induced PGE2 reduces Na+/K+ ATPase activity in Caco-2 cells via PKC, NF-κB and NO

The epinephrine-induced PGE2 reduces Na+/K+ ATPase activity in Caco-2 cells via PKC, NF-κB and NO

A Retrospective Trial Exploring Erzhu Yiren Decoction in Gastric Ulcer with Spleen Deficiency and Dampness-Heat

FTY720P Upregulates the Na+/K+ ATPase in HepG2 Cells by Activating S1PR3 and Inducing PGE2 Release

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